Inhibitors of Bacillus anthracis acetohydroxyacid synthase

Twelve compounds (100 μM) had a predicted log P between −0.5 and −3.0 and inhibited AHAS activity by >40%. CE, IQ, and SMM showed dose-dependent inhibition of Bacillus anthracis AHAS (BAntx AHAS) with IC50 values of 7.01 ± 0.81, 6.97 ± 0.44, and 10.02 ± 1.42 μM, respectively. CE and IQ were noncompetitive and uncompetitive inhibitors of BAntx AHAS with Kii values of 3.77 and 2.02, respectively. The order of potency towards BAntx AHAS was CE > PSE > MSM > TSM > SMM for sulfonylureas and IQ > Imazapic > IP for imidazolinones. The most active compound, CE, showed the lowest total interaction energy and highest MolDock score of −140.054 kcal/mol and −141.52, respectively. Three hydrogen bonds were identified between BAntx AHAS and CE. AHAS appears to be a promising potential target for new anti-anthracis drugs.